NIH Collaboratory Trials

May 13, 2024: Ongoing Funding Opportunity Supports Studies of Implementation and Sustainability of Interventions

Posted on by Damon Seils

NIH logoAn ongoing funding opportunity from the National Institutes of Health (NIH) is supporting dissemination and implementation research in health. The purpose of the funding opportunity is “to support studies that will identify, develop, and/or test strategies for overcoming barriers to the adoption, adaptation, integration, scale-up, and sustainability of evidence-based interventions, practices, programs, tools, treatments, guidelines, and policies.”

Posttrial sustainment and deimplementation of study interventions has been a focus of the NIH Collaboratory’s Implementation Science Core. In a recent article, investigators from 6 of the program’s completed pragmatic clinical trials summarized the posttrial interpretation of their trials’ results and considered the factors that influenced the sustainment or deimplementation of the studies’ interventions.

The article was published early this year in the Journal of General Internal Medicine.

Three lessons emerged from the review:

  • Ineffective interventions may be sustained if they have other measured or perceived benefits.
  • Effective interventions may not be sustained if they require significant resources.
  • Alignment with policy incentives is essential for achieving sustainment and scale-up of effective interventions.

Read about the NIH funding opportunity for research that supports the dissemination and implementation of evidence-based interventions.

April 18, 2024: New Living Textbook Chapter Articulates How Investigators Navigated Unexpected Challenges During Pragmatic Clinical Trials

Posted on by Karen Staman

During the course of the years-long pragmatic clinical trials supported by the NIH Pragmatic Trials Collaboratory, many unanticipated challenges have occurred, some of which have had profound effects on usual care, trial implementation, data systems, and staff. These unanticipated changes threatened the ability of the trials to address the questions they were designed to answer. A new chapter of the Living Textbook—Navigating the Unknown—describes these challenges and the responses of the study teams.

The chapter describes 3 general categories of challenges, each meriting a different response:

  1. If the challenge is a local or temporary issue (for example, a pandemic temporarily shuts down in-person care, or a partnering health system dissolves or is purchased), but the question is still relevant or important and the trial is still feasible, then a workaround may solve the problem.
  2. If the trial is no longer feasible for some reason (for example, the recruitment process is not feasible, or the intervention cannot be delivered as planned), and the question is still relevant, it is necessary to make significant changes to the protocol.
  3. If the question is no longer relevant or important (for example, new evidence or policy changes make the question no longer relevant), the trial should not continue. For this challenge, it may necessary either to stop the trial or to make fundamental changes to address a different question (since the original question is no longer relevant).

The chapter describes local or temporary challenges some of the study teams faced, such as the COVID-19 pandemic, health system mergers, and changes to the electronic health record (EHR). In these cases, the research questions were still relevant and important and the trial designs were still feasible, so workarounds were created to solve the problems.

  • Section 2: Study teams responded to staff turnover, leadership changes, and health system acquisitions and mergers.
  • Section 3: Rapid technology change created unexpected consequences, such as EHR updates causing system changes that affected intervention delivery, and sites switching EHRs systems creating complexities during the trial.
  • Section 4: COVID-19 had significant impacts on trial activities.

Section 5 of the new chapter addresses barriers that resulted from aspects of the protocol that could have impacted recruitment, retention, or implementation in a way that imperiled the ability of trials to answer the question posed by a research study. In these scenarios, researchers found it appropriate to change the protocol or research question—to pivot—in order to glean meaningful, actionable evidence.

Sections 6 and 7 describe challenges that can fall into either category 1 or 2, and investigators had to decide how to respond in real time.

  • Section 6: Clinical practice guidelines and policies changed due to new evidence from observational studies, small trials, and shifting expert opinion, and therefore, usual care changed.
  • Section 7: Quality improvement initiatives were launched to address similar problems, threatening the ability to discern differences between arms of the trial.

The NIH Pragmatic Trials Collaboratory supports pragmatic clinical trials embedded in healthcare systems to test interventions that address urgent public health problems faced by delivery systems. They involve hundreds to thousands of participants and generally include usual care as a control arm. One of the most important lessons learned through the course of these trials is that unexpected change is a given.

For more, see the section on Unanticipated Changes in the Analysis Plan chapter of the Living Textbook.

April 10, 2024: Primary Results of PRIM-ER Trial to Be Featured in This Week’s PCT Grand Rounds

Posted on by Damon Seils
Headshot of Dr. Corita Grudzen
Dr. Corita Grudzen, principal investigator of PRIM-ER

In this Friday’s PCT Grand Rounds, Corita Grudzen of the Memorial Sloan Kettering Cancer Center will present “Primary Palliative Care for Emergency Medicine, a Cluster Randomized Stepped-Wedge Trial Across 33 Emergency Departments,” including the results of the PRIM-ER trial.

The Grand Rounds session will be held on Friday, April 12, 2024, at 1:00 pm eastern.

Grudzen is a professor of emergency medicine at Weill Cornell Medical College and the Fern Grayer Chair in Oncology Care and the Patient Experience and division head of supportive and acute care services at the Memorial Sloan Kettering Cancer Center.

PRIM-ER, an NIH Collaboratory Trial, is a stepped-wedge, cluster randomized trial testing a multidisciplinary primary palliative care intervention in a diverse mix of emergency departments in the United States. The study is supported within the NIH Pragmatic Trials Collaboratory by a cooperative agreement from the National Institute on Aging. Read more about PRIM-ER.

Join the online meeting.

April 4, 2024: ICD-Pieces Trial Sees No Reduction in Hospitalization for Patients With Chronic Kidney Disease

Posted on by Damon Seils
Dr. Miguel Vazquez, principal investigator for ICD-Pieces

A primary care intervention for patients with coexisting chronic kidney disease, type 2 diabetes, and hypertension did not reduce the hospitalization rate for these patients when compared to usual care, according to the ICD-Pieces study.

The results of the study were published this week in the New England Journal of Medicine.

ICD-Pieces, an NIH Collaboratory Trial, was a cluster randomized, pragmatic clinical trial testing an intervention that used an electronic health record–based algorithm and practice facilitators in 141 primary care practices. The study team randomly assigned more than 11,000 adults to receive either the intervention or usual care. The large, diverse study population—of whom 20% were Black and almost 20% were Hispanic or Latino—was representative of the population with chronic kidney disease, type 2 diabetes, and hypertension in the United States.

In the intervention group, the study team used an algorithm to identify patients in the electronic health record in real time. Practice facilitators then worked with the participating primary care providers and patients to meet blood pressure targets, promote use of appropriate medications, achieve goals for blood glucose control, and engage in other guideline-directed care. The intervention period lasted 12 months, and the primary outcome was hospitalization for any reason.

At the end of the study, the hospitalization rate was similar between the intervention group and the usual care group. Rates of key secondary outcomes, such as emergency department visits and cardiovascular events, were also similar between the groups.

Read the full article.

“Although we did not observe a difference in the primary outcome, we believe the study is an important step in advancing our understanding of how to conduct pragmatic trials embedded in healthcare systems,” said Dr. Miguel Vazquez, the principal investigator for ICD-Pieces and a professor of internal medicine at UT Southwestern Medical Center in Dallas.

The study team identified and enrolled a large number of patients, including a large proportion of patients who are members of racial and ethnic groups that are usually underrepresented in clinical trials, Vazquez explained. Moreover, the intervention was delivered across 4 large healthcare systems using a variety of electronic health record systems, there was fidelity in intervention delivery, and there was robust capture of outcomes in a diverse population with multiple chronic conditions.

Vazquez also emphasized the value of conducting the ICD-Pieces study as an NIH Collaboratory Trial.

“The opportunity to work within the NIH Pragmatic Trials Collaboratory was essential for the successful completion of our trial,” Vazquez said. “Access to the expertise from the Coordinating Center and ongoing interactions with investigators from other projects provided critical knowledge to conduct our study embedded in large health systems,” he added.

ICD-Pieces is supported within the NIH Pragmatic Trials Collaboratory by a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases.

Learn more about ICD-Pieces.

February 26, 2024: In PRIM-ER Qualitative Study, EM Talk Program Improved Serious Illness Conversation Skills

Posted on by Damon Seils
Dr. Oluwaseun Adeyemi, lead author of the report

Communication skills training using the EM Talk model reached a high proportion of clinicians in participating emergency departments and improved their serious illness conversation skills, according to a qualitative study conducted as part of the PRIM-ER trial. The observed reach and effectiveness of the training program has the potential to improve use of these skills in clinical practice.

The results of the study were published last week in BMC Palliative Care.

PRIM-ER, an ongoing NIH Collaboratory Trial, is a stepped-wedge, cluster randomized trial testing a multidisciplinary primary palliative care intervention in a diverse mix of emergency departments in the United States. The intervention consists of education, clinical decision support, and other elements and is intended to improve the delivery of goal-directed emergency care of older adults.

The PRIM-ER intervention includes, among other elements, communication skills training and simulation workshops for emergency medicine clinicians using the EM Talk training program. The program is designed to improve serious illness conversation skills for emergency medicine physicians and advanced practice providers.

The authors of the report, led by Oluwaseun Adeyemi of New York University, under the guidance of principal investigators Corita Grudzen and Keith Goldfeld, found that 85% of emergency medicine physicians and advanced practice providers across 33 emergency departments completed the EM Talk training. In course evaluations completed after the training, participants reported that the training improved their serious illness conversation skills and their attitude toward engaging patients in serious illness conversations. Participants also reported that the training encouraged them to commit to using these skills in clinical practice.

A previously published study by the PRIM-ER research team reported the reach and effectiveness of a related training program for emergency nurses.

PRIM-ER is supported within the NIH Pragmatic Trials Collaboratory by a cooperative agreement from the National Institute on Aging. Read more about PRIM-ER.

February 6, 2024: Racial and Ethnic Minority Injury Survivors See Greater Improvements in PTSD Symptoms in the TSOS Study

Posted on by Damon Seils

Cover of the journal Trauma Surgery & Acute Care OpenInjury survivors from racial and ethnic minority groups experienced greater improvements than White injury survivors in their posttraumatic stress disorder (PTSD) symptoms after receiving a stepped collaborative care intervention. This was the finding of a secondary analysis of data from the Trauma Survivors Outcomes and Support (TSOS) study, an NIH Pragmatic Trials Collaboratory Trial led by principal investigator Doug Zatzick of the University of Washington.

The report was published online in Trauma Surgery & Acute Care Open.

In the TSOS study's main analysis, which was published in JAMA Surgery in 2021, the researchers saw a significant reduction in PTSD symptoms at 6 months in the intervention group compared with the control group. In the new secondary analysis, they saw that reduction in symptoms among racial and ethnic minority patients but not among White, non-Hispanic patients.

The findings "suggest that the previously reported 6-month treatment effects derive predominantly from intervention-related PTSD symptom improvements in non-white/Hispanic patients," wrote author Khadija Abu and colleagues from the University of Washington and the University of California, Los Angeles.

The TSOS study, an NIH Collaboratory Trial, was a stepped-wedge, cluster randomized pragmatic clinical trial testing the delivery of a stepped collaborative care intervention vs usual care for injured patients with PTSD symptoms and comorbid conditions. The study was conducted at 25 level I trauma centers in the United States. Of the 635 patients in the trial, 350 were from racial backgrounds other than White—including 218 patients who identified as African American, 15 as American Indian or Alaska Native, 8 as Asian or Pacific Islander, and 109 as multiple or other races. One-hundred two patients were Hispanic.

Patients in the control group received usual care plus nurse notification about their high level of distress. Patients in the intervention group received collaborative care consisting of evidence-based medication, cognitive behavioral therapy, and case management.

The study team proposed a few possible explanations for their findings:

  • In addition to its universal components, the TSOS intervention and referral elements consisted of tailored components designed to address the needs of a multicultural patient population by incorporating social determinants of health.
  • Collaborative care models include shared decision-making approaches, which are thought to enhance patients' engagement in care in racial and ethnic minority populations and other underserved groups.
  • In the year before their injury, almost half of the white, non-Hispanic patients in the study had accessed mental health services, compared with only about a quarter of the non-White and Hispanic patients, suggesting that participation in the study improved access to mental health care for patients in racial and ethnic minority groups.

A commentary accompanying the article praised the TSOS research team for "taking important steps to care for adverse sequelae associated with traumatic injury," and noted that "these first steps represent giant leaps for health equity" for underserved populations.

The TSOS study was supported within the NIH Pragmatic Trials Collaboratory by a cooperative agreement from the National Institute of Mental Health and by the NIH Common Fund through a cooperative agreement from the Office of Strategic Coordination within the Office of the NIH Director. Learn more about the NIH Collaboratory Trials.

January 23, 2024: Ethics Consultation Documents Now Available for RAMP Trial

Posted on by Damon Seils

Ethics and regulatory onboarding documentation is now available for RAMP, one of the NIH Pragmatic Trials Collaboratory's newest pragmatic clinical trials. The documents include meeting minutes and supplementary materials summarizing recent discussions of ethics and regulatory issues associated with the study.

The consultation took place by video conference and included representation from the study's principal investigator and study team, members of the NIH Collaboratory's Ethics and Regulatory Core, NIH staff, and NIH Collaboratory Coordinating Center personnel.

The goal of RAMP is to evaluate the use of a 12-week mind-body skills training program for patients with pain, including a one-on-one session with a “whole health coach” followed by 11 weekly group sessions to include prerecorded expert-led education videos, mind-body skills training and practice, and group discussions.

Ethics and regulatory documentation for all of the NIH Collaboratory Trials is available on our Data and Resource Sharing page.

January 16, 2024: Ethics Consultation Documents Now Available for AIM-CP and MOMs Chat & Care Study

Posted on by Damon Seils

Ethics and regulatory onboarding documentation for 2 of the NIH Pragmatic Trials Collaboratory's newest trials is now available. The documents include meeting minutes and supplementary materials summarizing recent discussions of ethics and regulatory issues associated with the AIM-CP trial and the MOMs Chat & Care Study.

The consultations took place by video conference and included representation from the studies' principal investigators, members of the NIH Collaboratory's Ethics and Regulatory Core, NIH staff, and NIH Collaboratory Coordinating Center personnel.

AIM-CP will address test a care management program to address inequities in access to nonpharmacological treatment for chronic pain in rural populations.

The MOMs Chat & Care Study will test the effectiveness of an integrated care model approach at 2 levels of intensity designed to facilitate timely, appropriate care for Black patients to reduce their risk for severe maternal morbidity.

Ethics and regulatory documentation for all of the NIH Collaboratory Trials is available on our Data and Resource Sharing page.

January 11, 2024: BeatPain Utah Study Team Uses Implementation Mapping Approach to Plan Hybrid Trial

Posted on by Damon Seils

In a new article from the NIH Pragmatic Trials Collaboratory, the BeatPain Utah study team describes the "implementation mapping" they used to plan for trial implementation. The comprehensive, systematic approach enabled the team to craft an implementation plan for a complex telehealth intervention and to identify outcomes for evaluating the success of the implementation strategies.

The article was published this month in Implementation Science Communications.

BeatPain Utah, an NIH Collaboratory Trial, is studying real-world implementation of a telehealth physical therapy strategy for patients with chronic back pain in primary care clinics of federally qualified health centers. During the 1-year planning phase described in the article, the study team developed a logic model, based in part on the Consolidated Framework for Implementation Research (CFIR), to identify contextual factors across several domains that could influence e-referral and telehealth implementation in the trial.

In this ongoing type 1 hybrid effectiveness-implementation trial, the implementation strategies developed through the mapping exercise are being evaluated as part of the trial.

BeatPain Utah is supported within the NIH Pragmatic Trials Collaboratory through the NIH HEAL Initiative under an award administered by the National Institute of Nursing Research. Learn more about BeatPain Utah.

January 9, 2024: Ethics Consultation Documents Now Available for iPATH Trial

Posted on by Damon Seils

Ethics and regulatory onboarding documentation is now available for iPATH, one of the NIH Pragmatic Trials Collaboratory's newest pragmatic clinical trials. The documents include meeting minutes and supplementary materials summarizing recent discussions of ethics and regulatory issues associated with the study.

The consultation took place by video conference and included representation from the study's principal investigator and study team, members of the NIH Collaboratory's Ethics and Regulatory Core, NIH staff, and NIH Collaboratory Coordinating Center personnel.

The goal of iPATH is to refine and implement an approach to practice transformation that was originally conceived and pilot-tested to support federally qualified health centers (FQHCs) in their pursuit of National Committee for Quality Assurance recognition as patient-centered medical homes for patients with type 2 diabetes. The study will include extensive qualitative work to identify implementation factors in FQHCs that are diverse in terms of geography, race/ethnicity, and diabetes control performance; and to customize and comprehensively evaluate the implementation approach.

Ethics and regulatory documentation for all of the NIH Collaboratory Trials is available on our Data and Resource Sharing page.